Endogenous regulatory agents, controlling spontaneous uterine activity and reactivity to stimulants, act by facilitating or impeding the entry of activator-Ca ions to the myofilaments. Control of activator Ca ions, which couples excitation (membrane events) with contraction (a myoplasmic event), is evidently the most rational target for therapies aimed at regulation of the uterus. The agonists and antagonists of physiologcal and therapeutic interest act after occupancy of operationally defined receptors or high affinity, specific binding sites within the myometrium. This study will focus on the receptors located on the plasma membrane and hence most likely involved in regulating membrane function. Techniques will be developed to enable myometrial sarcolemma to be isolated in highly purified form by affinity adsorption to ligands immobilized on glass beads. Purified sarcolemma will be used to study prostaglandin, catecholamine and oxytocin receptors and specific Ca ions binding sites in uteri obtained in well defined physiological states. The binding studies will be related to an examination of the mobility of membrane Ca ions or to membrane permeability to interstitial Ca ions using intact cell in isolated uterine fragments. Similar tissue fragments will be cultured in vitro enabling detailed analysis of the dynamics of progesterone's action in modifying Ca-exchange. Numerous endocrine manipulations will be possible using the culture system in an attempt to understand hormonal control of the receptor populations in sarcolemma.